When does the lung die?K fc, cell viability, and adenine nucleotide changes in the circulation-arrested rat lung

1997 ◽  
Vol 83 (1) ◽  
pp. 247-252 ◽  
Author(s):  
David R. Jones ◽  
Randy M. Becker ◽  
Steve C. Hoffmann ◽  
John J. Lemasters ◽  
Thomas M. Egan
Keyword(s):  
Cell Viability ◽  
Time Course ◽  
Ischemia Reperfusion Injury ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Ischemia Reperfusion ◽  
Rat Lung ◽  
Donor Pool ◽  
Ischemic Time

Jones, David R., Randy M. Becker, Steve C. Hoffmann, John J. Lemasters, and Thomas M. Egan. When does the lung die? K fc, cell viability, and adenine nucleotide changes in the circulation-arrested rat lung. J. Appl. Physiol. 83(1): 247–252, 1997.—Lungs harvested from cadaveric circulation-arrested donors may increase the donor pool for lung transplantation. To determine the degree and time course of ischemia-reperfusion injury, we evaluated the effect of O2 ventilation on capillary permeability [capillary filtration coefficient ( K fc)], cell viability, and total adenine nucleotide (TAN) levels in in situ circulation-arrested rat lungs. K fc increased with increasing postmortem ischemic time ( r = 0.88). Lungs ventilated with O2 1 h postmortem had similar K fc and wet-to-dry ratios as controls. Nonventilated lungs had threefold ( P < 0.05) and sevenfold ( P < 0.0001) increases in K fc at 30 and 60 min postmortem compared with controls. Cell viability decreased in all groups except for 30-min postmortem O2-ventilated lungs. TAN levels decreased with increasing ischemic time, particularly in nonventilated lungs. Loss of adenine nucleotides correlated with increasing K fc values ( r = 0.76). This study indicates that lungs retrieved 1 h postmortem may have normal K fc with preharvest O2 ventilation. The relationship between K fc and TAN suggests that vascular permeability may be related to lung TAN levels.

Energy metabolism and adenine nucleotide degradation in twitch-stimulated rat hindlimb during ischemia-reperfusion

1993 ◽  
Vol 264 (4) ◽  
pp. E655-E661 ◽  
Author(s):  
D. G. Welsh ◽  
M. I. Lindinger
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Time Course ◽  
Ischemia Reperfusion Injury ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Ischemia Reperfusion ◽  
Control Period ◽  
High Energy ◽  
Nucleotide Degradation

The purpose of this study was to characterize twitch tension and energy metabolism in ischemic, stimulated rat hindlimb to determine its suitability as a rapid time course model of ischemia-reperfusion injury. After 15 min equilibration, rat hindlimbs were stimulated (1-Hz twitches, 0.2 ms pulse duration, 15 V) for 5 min (control, n = 8). This twitch protocol was maintained throughout the ischemic and reperfusion periods. The control period was followed by 5, 20, or 40 min of ischemia (ligation of femoral artery and vein) or 40 min of ischemia with 0, 5, or 20 min of reperfusion (removal of ligature). The soleus [89% slow oxidative (SO)] and the white gastrocnemius [WG; 91% fast glycolytic (FG)] were analyzed for phosphocreatine (PCr), adenine nucleotides, glycogen, and glycolytic intermediates. Ischemia was characterized by progressive decreases in twitch tension, high-energy phosphagens, total adenine nucleotides (TAN), and glycogen. Also, energy metabolism was altered at a greater rate in WG than in soleus. Reperfusion resulted in a recovery in PCr and lactate, with little change in ATP, TAN, or glycogen. The inability to resynthesize adenine nucleotides and glycogen during reperfusion is characteristic of damaged skeletal muscle. The extent of the metabolic alterations in SO and FG muscles during twitch stimulation was comparable with previously reported noncontracting ischemia protocols of 2-4 and 4-7 h in length, respectively. The present study demonstrates that twitch stimulation of ischemic skeletal muscle is a useful model for inducing rapid metabolic changes and an ischemic insult comparable to prolonged noncontracting ischemia-reperfusion models.

Static Inflation Attenuates Ischemia/Reperfusion Injury in an Isolated Rat Lung In Situ

CHEST Journal ◽  
2004 ◽  
Vol 126 (2) ◽  
pp. 552-558 ◽  
Author(s):  
Shang Jyh Kao ◽  
David Wang ◽  
Diana Yu-Wung Yeh ◽  
Kang Hsu ◽  
Yung Hsiang Hsu ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rat Lung ◽  
Isolated Rat Lung ◽  
Isolated Rat

Protective effects of glycine during hypothermic renal ischemia-reperfusion injury

1991 ◽  
Vol 261 (5) ◽  
pp. F841-F848 ◽  
Author(s):  
M. J. Mangino ◽  
M. K. Murphy ◽  
G. G. Grabau ◽  
C. B. Anderson
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Ischemia Reperfusion ◽  
Renal Tissue ◽  
Renal Ischemia ◽  
Cold Ischemia ◽  
Urine Production

The objective of this investigation was to test the effects of glycine, a cytoprotectant in normothermic in vitro models of renal ischemia, in a model of hypothermic renal preservation injury. This study also probes possible physiological mechanisms of glycine protection during renal hypothermic ischemia-reperfusion injury. Canine kidneys were subjected to 48 h of hypothermic ischemia (4 degrees C) after intravascular flush with cold conventional Collins solution (G. H. Collins, M. B. Bravo-Shugarman, and P. I. Terasaki, Lancet 2: 1219-1223, 1969) and were subsequently revascularized for 1 h. After 1 h of reperfusion, glomerular filtration rate, urine production, and electrolyte excretion were dramatically higher when the Collins flush contained 5 mM glycine, compared with the 0 mM glycine controls. Renal tissue adenine nucleotides and glutathione levels progressively declined with graded cold ischemia times, and glycine had no effect on these levels. However, renal tissue ATP levels (but not glutathione) were significantly higher when kidneys were flushed with glycine, stored for 48 h, and reoxygenated in vitro for 1 h at 37 degrees C, compared with kidneys flushed without glycine. Analysis of CoA esters from ischemic renal tissue indicated altered production of only butyryl CoA after 48 and 72 h of cold ischemia, but no differences were detected in glycine or control kidneys. In conclusion, this study reports dramatic functional preservation with glycine in kidneys subjected to hypothermic ischemia and in vivo reperfusion. The mechanisms of these effects appear not to be attributable to the maintenance of cellular adenine nucleotide or glutathione levels nor to the scavenging of accumulated amphipathic acyl CoA esters.

scholarly journals NORMOTHERMIC EXTRACORPOREAL PERFUSION IN SITU IN DECEASED ORGAN DONORS WITH IRREVERSIBLE CARDIAC ARREST AND ONE HOUR OF ASYSTOLE. 5-YEAR OUTCOMES OF KIDNEY TRANSPLANTATION

2016 ◽  
Vol 18 (3) ◽  
pp. 57-67
Author(s):  
A. E. Skvortsov ◽  
I. V. Loginov ◽  
A. A. Kukushkin ◽  
A. N. Ananiev ◽  
A. A. Kutenkov ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Ischemia Reperfusion Injury ◽  
Organ Procurement ◽  
Ischemia Reperfusion ◽  
Rejection Rate ◽  
Organ Donors ◽  
Ischemic Time ◽  
Transplant Program ◽  
State Research Institute

Aim.The global shortage of deceased organ donors caused increasing interest to the transplant program based on the use of organs from the donors with sudden irreversible cardiac arrest, or asystolic donors (DCD). Ischemia-reperfusion injury as a result of cardiac arrest remains a key problem that limits the use of organs from DCD. Our clinical study was intended to determine the acceptability of renal transplants derived from the DCD using extracorporeal perfusion in situ after 60 minutes of asystole.Materials and methods.In 2009–2014, St. Petersburg Organ Procurement Organization (OPO) obtained kidneys from 29 DCD with critically expanded warm ischemic time (WIT). The design of this study was approved by the Scientifi c Board and Ethics Committee of the State Research Institute for Emergency Medicine (Decision 7/0615/09). Initially, no one of died patients was considered as potential organ donors. In case of failed advanced CPR the death of a patient was declared initiating the protocol of subnormothermic extracorporeal abdominal perfusion with ECMO, thrombolytics (strepokinase 1.5 mln U), and LD. The procedures were established by the authorized OPO team which arrived with perfusion equipment in 30–40 minutes after declaration of donors’ death. Mean WIT was 58.1 (19.39) minutes (Mean (SD). Resuscitated grafts were transplanted into 58 recipients. The outcomes of transplantation of resuscitated kidneys were compared to those of 112 KTx from 115 brain death donors (BDDs).Results.Immediate functioning of kidney grafts was observed in 28 (48.3%) of 58 recipients. There were 4 cases of primary graft non-function. By the end of the fi rst post-transplant year there was an acute rejection rate of 12.1% (9 episodes of rejection) in the DCD group vs. 23.2% (26 episodes of rejection) in the BDD group (p < 0.05). The actuarial 5-year graft survival rate was 82.8% (n = 48) in DCD group, and 87.5% (n = 98) in BDD group (p > 0.05). Creatinine levels at the end of the fi fth year were 0.094 (0.06) and 0.103 (0.07) mmol/l in DCD and BDD groups, respectively (p > 0.05).Conclusions.Kidneys from DCDs with critically expanded WIT could be successfully used for transplantation if in situ organ “resuscitation” perfusion procedures are included into procurement protocol. The 5-year outcomes meet the generally accepted criteria for grafts’ and recipients’ rates of survival and functioning. This approach could substantially expand the organ donors’ pool. 

scholarly journals LncRNA LSINCT5/miR-222 regulates myocardial ischemia‑reperfusion injury through PI3K/AKT pathway

2021 ◽  
Author(s):  
Xueying Tong ◽  
Jiajuan Chen ◽  
Wei Liu ◽  
Hui Liang ◽  
Hezhong Zhu
Keyword(s):  
Myocardial Ischemia ◽  
Cell Viability ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Akt Pathway ◽  
Akt Signaling Pathway ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

AbstractCardiovascular diseases rank the top cause of morbidity and mortality worldwide and are usually associated with blood reperfusion after myocardial ischemia/reperfusion injury (MIRI), which often causes severe pathological damages and cardiomyocyte apoptosis. LSINCT5 expression in the plasma of MI patients (n = 53), healthy controls (n = 42) and hypoxia-reoxygenation (HR)-treated cardiomyocyte AC16 cells was examined using qRT-PCR. The effects of LSINCT5 on cell viability and apoptosis were detected by MTT and flow cytometry, respectively. The expression of apoptosis-related proteins Bcl2, Bax and caspase 3 were tested by Western blot. The interaction between LSINCT5 and miR-222 was predicted by bioinformatic analysis. Moreover, changes in viability and apoptosis of AC16 cells co-transfected with siLSINCT5 and miR-222 inhibitor after HR treatment were examined. At last, the expression of proteins in PI3K/AKT pathway, namely PTEN, PI3K and AKT, was examined to analyze the possible pathway participating in LSINCT5-mediated MI/RI. Our study showed that LSINCT5 expression was upregulated in the plasma of MI patients and HR-treated AC16 cells. LSINCT5 overexpression significantly decreased cell viability and apoptosis. Luciferase reporter gene assay and RNA pulldown assay showed that LSINCT5 was a molecular sponge of miR-222. MiR-222 silencing in AC16 cells simulated the phenotypes of MIRI patients and HR-treated cells, indicating that LSINCT5 functions via miR-222 to regulate proliferation and apoptosis of HR-treated AC16 cells. We also showed that proteins of PI3K/AKT signaling pathway were affected in HR-treated AC16 cells, and LSINTC5 knockdown rescued these effects. LncRNA LSINCT5 was upregulated during MI pathogenesis, and LSINCT5 regulated MIRI possibly via a potential LSINCT5/miR-222 axis and PI3K/AKT signaling pathway. Our findings may provide novel evidence for MIRI prevention.

scholarly journals Reducing Cardiac Injury during ST-Elevation Myocardial Infarction: A Reasoned Approach to a Multitarget Therapeutic Strategy

2021 ◽  
Vol 10 (13) ◽  
pp. 2968
Author(s):  
Alessandro Bellis ◽  
Giuseppe Di Gioia ◽  
Ciro Mauro ◽  
Costantino Mancusi ◽  
Emanuele Barbato ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Reperfusion Injury ◽  
Therapeutic Strategy ◽  
Ventricular Remodeling ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
St Elevation Myocardial Infarction ◽  
Ischemic Time ◽  
St Elevation

The significant reduction in ‘ischemic time’ through capillary diffusion of primary percutaneous intervention (pPCI) has rendered myocardial-ischemia reperfusion injury (MIRI) prevention a major issue in order to improve the prognosis of ST elevation myocardial infarction (STEMI) patients. In fact, while the ischemic damage increases with the severity and the duration of blood flow reduction, reperfusion injury reaches its maximum with a moderate amount of ischemic injury. MIRI leads to the development of post-STEMI left ventricular remodeling (post-STEMI LVR), thereby increasing the risk of arrhythmias and heart failure. Single pharmacological and mechanical interventions have shown some benefits, but have not satisfactorily reduced mortality. Therefore, a multitarget therapeutic strategy is needed, but no univocal indications have come from the clinical trials performed so far. On the basis of the results of the consistent clinical studies analyzed in this review, we try to design a randomized clinical trial aimed at evaluating the effects of a reasoned multitarget therapeutic strategy on the prevention of post-STEMI LVR. In fact, we believe that the correct timing of pharmacological and mechanical intervention application, according to their specific ability to interfere with survival pathways, may significantly reduce the incidence of post-STEMI LVR and thus improve patient prognosis.

Overexpression of miR-431 attenuates hypoxia/reoxygenation-induced myocardial damage via autophagy-related 3

2020 ◽  
Author(s):  
Kang Zhou ◽  
Yan Xu ◽  
Qiong Wang ◽  
Lini Dong
Keyword(s):  
Cell Viability ◽  
Cell Apoptosis ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Protective Role ◽  
Human Cardiomyocytes ◽  
Hypoxia Reoxygenation

Abstract Myocardial injury is still a serious condition damaging the public health. Clinically, myocardial injury often leads to cardiac dysfunction and, in severe cases, death. Reperfusion of the ischemic myocardial tissues can minimize acute myocardial infarction (AMI)-induced damage. MicroRNAs are commonly recognized in diverse diseases and are often involved in the development of myocardial ischemia/reperfusion injury. However, the role of miR-431 remains unclear in myocardial injury. In this study, we investigated the underlying mechanisms of miR-431 in the cell apoptosis and autophagy of human cardiomyocytes in hypoxia/reoxygenation (H/R). H/R treatment reduced cell viability, promoted cell apoptotic rate, and down-regulated the expression of miR-431 in human cardiomyocytes. The down-regulation of miR-431 by its inhibitor reduced cell viability and induced cell apoptosis in the human cardiomyocytes. Moreover, miR-431 down-regulated the expression of autophagy-related 3 (ATG3) via targeting the 3ʹ-untranslated region of ATG3. Up-regulated expression of ATG3 by pcDNA3.1-ATG3 reversed the protective role of the overexpression of miR-431 on cell viability and cell apoptosis in H/R-treated human cardiomyocytes. More importantly, H/R treatments promoted autophagy in the human cardiomyocytes, and this effect was greatly alleviated via miR-431-mimic transfection. Our results suggested that miR-431 overexpression attenuated the H/R-induced myocardial damage at least partly through regulating the expression of ATG3.

Decline of contractility during ischemia-reperfusion injury: actin glutathionylation and its effect on allosteric interaction with tropomyosin

2006 ◽  
Vol 290 (3) ◽  
pp. C719-C727 ◽  
Author(s):  
Frank C. Chen ◽  
Ozgur Ogut
Keyword(s):  
Reperfusion Injury ◽  
Posttranslational Modifications ◽  
Actin Polymerization ◽  
Time Course ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
High Concentration ◽  
Cross Sectional ◽  
The Impact

The severity and duration of ischemia-reperfusion injury is hypothesized to play an important role in the ability of the heart subsequently to recover contractility. Permeabilized trabeculae were prepared from a rat model of ischemia-reperfusion injury to examine the impact on force generation. Compared with the control perfused condition, the maximum force (Fmax) per cross-sectional area and the rate of tension redevelopment of Ca2+-activated trabeculae fell by 71% and 44%, respectively, during ischemia despite the availability of a high concentration of ATP. The reduction in Fmax with ischemia was accompanied by a decline in fiber stiffness, implying a drop in the absolute number of attached cross bridges. However, the declines during ischemia were largely recovered after reperfusion, leading to the hypothesis that intrinsic, reversible posttranslational modifications to proteins of the contractile filaments occur during ischemia-reperfusion injury. Examination of thin-filament proteins from ischemic or ischemia-reperfused hearts did not reveal proteolysis of troponin I or T. However, actin was found to be glutathionylated with ischemia. Light-scattering experiments demonstrated that glutathionylated G-actin did not polymerize as efficiently as native G-actin. Although tropomyosin accelerated the time course of native and glutathionylated G-actin polymerization, the polymerization of glutathionylated G-actin still lagged native G-actin at all concentrations of tropomyosin tested. Furthermore, cosedimentation experiments demonstrated that tropomyosin bound glutathionylated F-actin with significantly reduced cooperativity. Therefore, glutathionylated actin may be a novel contributor to the diverse set of posttranslational modifications that define the function of the contractile filaments during ischemia-reperfusion injury.

Abstract 17188: Cryoem Analysis in Cardiac Isolated Mitochondria Reveals New Insights for CsA and mPTP Activation

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Jasiel O Strubbe ◽  
Jason Schrad ◽  
James F Conway ◽  
Kristin N Parent ◽  
Jason N Bazil
Keyword(s):  
Time Course ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Necrosis ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Granule Formation ◽  
Membrane Rupture ◽  
Mptp Opening

Excessive Ca 2+ accumulation is the main source of cardiac tissue and cell death during myocardial ischemia-reperfusion injury (IR injury) and myocardial infarction. Calcium dysregulation and overload leads to mitochondrial dysfunction, excessive reactive oxygen species (ROS) production, catastrophic energy failure, and opening of the cyclosporine A-sensitive mitochondrial permeability transition pore (mPTP). Mitochondrial Ca 2+ accumulation also results in the formation of amorphous Ca 2+ -phosphate granules localized in the mitochondrial matrix. These amorphous electron-dense granules are main components of the mitochondrial Ca 2+ sequestration and buffering system by mechanisms not yet well understood. The two aims of the present study are to test the relationship of Ca 2+ -phosphate granule size and number in cardiac mitochondria 1) exposed to a bolus calcium sufficient to elicit permeabilization and 2) whether CsA-treated mitochondria alters granule formation and size. A time course series of CryoEM images was analyzed to follow the permeabilization process. CryoEM results showed that mitochondrial incubated for longer time-courses have increased number of small granules (40 - 110 nm), swelling, membrane rupture and induction of mPTP opening. Conversely, shorter incubation time resulted in less granules per mitochondrion yet of similar size (35 - 90 nm). CsA- treated mitochondria, on the other hand, showed bigger phosphate granules (120 - 160 nm), and both lower granules per mitochondria and mPTP opening susceptibility. These results suggest a novel mechanism for CsA in which Ca 2+ -phosphate granule sizes are enhanced while maintaining fewer per mitochondrion. This effect may explain why CsA-treated mitochondria have higher calcium tolerance, delayed Ca 2+ -dependent opening of the mPTP, and protects against reperfusion-induced myocardial necrosis.

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